Disrupted electrical signalling in the brain may contribute to the accumulation of amyloid-β (Aβ) protein, a hallmark of Alzheimer’s disease (AD), suggests a study in mice published in Nature this week. The study shows that restoring the electrical oscillations generated by neural circuits reduces Aβ formation and activates immune cells to clear the protein from the brain.
When networks of neurons are activated in a synchronised manner in the brain, they generate electrical oscillations. If the frequency of these brain rhythms averages 40 per second (Hz), they are referred to as gamma oscillations. Gamma oscillations are thought to be important for higher cognitive functions and sensory responses and previous studies have shown they are disrupted in various neurological diseases, including AD. However, how gamma oscillations affect pathology has remained unclear.
Li-Huei Tsai and colleagues recorded the neural activity of mice in a well-established model of AD to show that gamma oscillations declined before Aβ accumulated to form amyloid plaques and before cognitive decline. They then used an optogenetic (light-mediated) technique to directly stimulate neurons in the hippocampus of AD model mice to produce gamma oscillations, which reduced Aβ production in this region of the brain and led to the activation of microglia, the brain’s immune cells, to clear Aβ. The authors devised a non-invasive approach to induce gamma oscillations in the mouse primary visual cortex by flickering LED lights at 40 Hz. This non-invasive technique reduced Aβ levels in the visual cortex of mice with early stages of AD and decreased the amount of amyloid plaque in the visual cortex of aged mice at a later stage of disease.
Taken together, these observations suggest that the reduction of total Aβ levels may be mediated by both decreased Aβ formation and increased amyloid clearance by microglia. However, the authors note that using gamma oscillations therapeutically would constitute a fundamentally different approach to prior AD therapies, so further study is needed to determine whether this approach will work in humans.